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High-Sensitivity Troponin Making Inroads as Tests Hit US Market

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NEW YORK (360Dx) – High-sensitivity troponin testing continues to make inroads in the US as diagnostic firms bring new high-sensitivity assays to market.

Mathias Egermark, senior VP/lifecycle leader cardiac, women's health, personalized healthcare solutions at Roche, said he expects that essentially all of the company's US troponin T customers will convert to the high-sensitivity version of the assay over the next two to three years.

That would roughly track the company's experience worldwide. Roche launched its high-sensitivity troponin T assay globally (excluding the US) in 2009 with more or less 100 percent of its troponin customers converting to the high-sensitivity test by 2012, Egermark said.

With this adoption of high-sensitivity testing, diagnostics firms and clinicians are exploring whether troponin testing could prove useful in applications beyond its traditional role of helping to assess whether a patient has suffered a heart attack.

Roche was the first to the US market with a high-sensitivity troponin assay, launching the test in 2017. Siemens and Beckman Coulter followed with US Food and Drug Administration clearance for their own high-sensitivity troponin tests last year.

Alan Wu, professor of laboratory medicine at University of California, San Francisco, and clinical chemistry laboratory chief at Zuckerberg San Francisco General Hospital, said that uptake of the tests has tracked availability, with adoption of the Roche assay "quite a bit more advanced" than that of the Siemens and Beckman Coulter tests.

The Roche tests measures levels of the protein troponin T, whereas the Siemens and Beckman Coulter tests measure levels of troponin I. Wu noted that the two biomarkers exhibit some different behaviors — for instance, he said, the body clears troponin T from the blood slightly slower than it does troponin I, and patients with renal disease may release higher levels of troponin T than I — but the differences are generally not substantial enough to drive labs to adopt one over the other.

Instead, Wu said, labs will likely adopt whatever high-sensitivity assay becomes available on their clinical instrumentation.

"You either have Roche equipment, in which case you are obligated to use troponin T, or you have equipment from Beckman or Siemens, in which case you use troponin I," he said. "A lab director wouldn't purchase an instrument just to select a [high-sensitivity] troponin assay. The differences in the performance of the two assays are not sufficient to justify one over the other."

Labs running instrumentation without a high-sensitivity troponin option are typically waiting for one to become available on their platform rather than purchase instrumentation from a vendor that does offer a high-sensitivity test.

Robert Christenson, medical director of the core laboratories at the University of Maryland Medical Center, noted that his facility is waiting for a high-sensitivity test to become available on its Ortho Clinical Diagnostics instrumentation.

"We're actually involved with [Ortho Clinical's] FDA trial, but it's not completed yet," he said. "Then it has to go through FDA, and FDA can take years. Hopefully, it won't take years for us, but we'll see."

The speed with which a lab moves into high-sensitivity testing also depends on the patient populations it serves, said Dina Greene, assistant professor and associate director, chemistry, at the University of Washington Department of Laboratory Medicine.

Greene's lab uses Beckman Coulter instrumentation and so has access to a high-sensitivity troponin assay, but she said she and her colleagues have not moved to a high-sensitivity assay due to the fact that they largely work with urgent care and primary care practices rather than emergency departments.

"I think it definitely will be some that we will integrate [into the lab], but it's not a priority the way it would be if I was at a large university or large community hospital with a large emergency department," she said. "If I was at a 400-bed hospital with an emergency department that had a lot of people presenting with chest pain, then I would be inclined to be more aggressive about rolling it out."

UCSF's Wu said that the process and cost of running a high-sensitivity troponin test for a lab are essentially unchanged from standard troponin assays but that implementing the test nonetheless requires substantial work, particularly around making sure clinicians are aware of changes in the way test results are reported and what they mean.

"With high-sensitivity, we are switching the units from nanograms per milliliter to nanograms per liter, and so a [concentration of] .04 becomes 40, a .003 becomes 3," he said. "The [doctors] need to understand that, and there needs to be communication well in advance, because the last thing you want to see is somebody misinterpreting a troponin value as being high when it isn't, leading to unnecessary treatment like cardiac catheterization."

This may seem like a relatively simple issue, but it requires careful coordination between the lab and clinicians, said James Januzzi, a cardiologist at Massachusetts General Hospital, which was one of the first institutions in the US to roll out high-sensitivity troponin testing.

"It's critically important that there is coordination across all the involved parties so that everyone understands that the change is coming, what the factors necessary to understand are, and when the change occurs that everyone is prepared for the differences in how the assay is measured and how it is interpreted," he said.

Another consideration for clinical labs is the different time points at which high-sensitivity versus traditional troponin tests are performed, Januzzi said, noting that because high-sensitivity test scores will change more rapidly in heart attack patients than traditional test scores, faster turnaround time is required.

A standard troponin testing protocol typically tests at baseline then at six and 12 hours, but high-sensitivity protocols more commonly test at baseline and then at one and two hours, he said.

Additionally, doctors will need the result of the first test before they draw blood for the second test, he noted. "It makes no sense to deliver an assay result after the second blood draw has already been sent to the lab."

"Time is of the essence, so being able to handle samples in random access fashion as they fly in from the emergency department will be necessary," Januzzi said. "Coordinating with the emergency department in order to be ready for that change is crucially important."

There are also questions in the field around whether clinicians should use sex-specific cutoffs with the high-sensitivity tests. Healthy women typically have lower troponin levels than healthy men, which Greene said suggests the cut-offs for testing should be different for women and men.

This issue has become more relevant with the adoption of high-sensitivity testing "because the detection at the low-end allows us to resolve the differences between men and women," she said.

That women have historically been underdiagnosed for heart attacks compared to men is a key factor driving interest in sex-specific cut-offs for high sensitivity tests, Christenson said, though he noted that while healthy troponin values in women and men are different, values in both sexes are "remarkably similar" in cases of myocardial infarction (MI).

While the high sensitivity of the new assays has enhanced detection of heart attacks, it has also complicated this detection, Januzzi said.

"When troponin was a lousy assay, it was a great test," he said. "If it was abnormal, patients probably had an MI."

High-sensitivity assays, on the other hand, are less specific for MI as they are able to detect low but elevated levels of troponin that can often indicate cardiac injury due to other factors like chronic kidney disease or infection.

"So, there are times when we need to extend our diagnostic evaluation to try to better understand whether this [elevated troponin] is from an MI or from some other cause," Januzzi said.

He said that Mass General has not seen an increase in inappropriate admissions or inappropriate testing since launching high-sensitivity troponin testing.

Wu noted, however, that while there is fairly solid agreement among experts and at leading medical centers about how to evaluate high-sensitivity troponin results, it could be more problematic in the community setting.

"There's little debate amongst the experts of how to use troponin," he said. "The gap is not at the key opinion leader end. It's with, for instance, the emergency department physician in a community hospital who isn't a specialist in cardiac disease and who has to deal with literally dozens of other medical conditions that they might see in a given day and who may only be seeing one or two patients where this is even relevant. They may not be up to speed about how a particular biomarker is to be interpreted."

A recent study by researchers at University Hospital Southampton found that 1 in 20 hospital patients had troponin levels above the high-sensitivity cut-offs, including patients with no cardiac complaints. The findings highlighted "the need for clinical staff to interpret hs-cTnI concentrations carefully and systematically when making a diagnosis of acute myocardial infarction," the authors wrote. 

But while the sensitivity of these assays can make MI diagnosis more complicated, it also opens up the possibility of new applications for troponin testing.

Roche's Egermark said, for example, that high-sensitivity troponin T has been shown to be useful as part of risk assessment panels for patients with coronary artery disease and atrial fibrillation patients receiving anti-coagulant treatment.

A recent study by Baylor College of Medicine researchers found that high-sensitivity troponin measurements could help assess risk of cardiac events in asymptomatic patients.

"I think [high-sensitivity troponin] could have applications in primary care, for sure," UW's Greene said. "It could be seen as just a marker of cardiac health."